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Purine nucleoside phosphorylase inhibitors (PNP-Is) were developed to ablate transformed lymphocytes. However, only some patients with leukemia benefit from PNP-Is. We provide a molecular explanation: the deoxyribonucleoside triphosphate (dNTP) hydrolase SAM and HD domain-containing protein 1 (SAMHD1) prevents the accumulation of toxic dNTP levels during purine nucleoside phosphorylase inhibition. We propose PNP-Is for targeted therapy of patients with acquired SAMHD1 mutations.

Original publication

DOI

10.1080/23723556.2020.1804308

Type

Journal article

Journal

Mol Cell Oncol

Publication Date

20/09/2020

Volume

7

Keywords

CLL, PNP, SAMHD1, forodesine, leukemia